Saccharomyces cerevisiae, or baker's yeast, is widely used as a host for the expression of a variety of heterologous polypeptides. Many different proteins from a variety of species have been expressed in S. cerevisiae, some to levels of >10% of total cell protein. Typically, expression has been mediated by a plasmid containing a DNA sequence encoding the heterologous polypeptide and the gene control region that controls gene expressions in S. cerevisiae as well as other sequences required for the selection and amplification of the plasmid in both S. cerevisiae and in Escherichia coli. Alternatively, it is also possible to integrate the coding sequence and the gene control region into a S. cerevisiae chromosome and achieve high-level expression.
The gene control regions utilized in the expression of heterologous polypeptides in S. cerevisiae are typically those which naturally occur in S. cerevisiae, e.g., the gene control region for the expression of the divergent GAL1 and GAL10 genes. In contrast, heterologous gene control regions, when used in S. cerevisiae cells, have generally been found to be inactive, or lead to aberrant initiation of transcription. It has been proposed that use of S. cerevisiae gene control regions is essential for the efficient expression of heterologous genes in S. cerevisiae cells. (Romanos et al., YEAST 8:423-488 (1992)).
The references cited herein are not admitted to be prior art to the claimed invention.